The Fischer-Kiliani synthesis is one of several procedures available for one-carbon homologation of monosaccharides. This synthesis involves the addition of the elements of HCN to aldehydes to afford, generally, an epimeric pair of cyanohydrins, with the nitrile group of the latter subsequently being reduced under conditions where hydrolysis of the formed imine to its corresponding aldose prevails, as shown by the equation, EQU --CHO+HCN.fwdarw.--CHOHCN.fwdarw.--CHOHCHO
We recently have shown in U.S. Pat. No. 4,581,447 that this approach provides an effective entry into the family of L-sugars, although several aspects of the synthesis required new developments before commercial feasibility became a reality.
The transformation of the intermediate cyanohydrin to its corresponding aldehyde is a curious one involving two consecutive reactions and requiring quite high discrimination among several reaction pathways. What is required is the reduction of the nitrile group to an imine followed by rapid hydrolysis of the imine to its corresponding aldehyde with minimal hydrogenation of the imine to its amine and of the aldehyde to its alcohol. ##STR1##
In the context of competing reactions the requirements for selectivity are that k.sub.i &gt;&gt;k'.sub.a, k.sub.h &gt;&gt;k.sub.a [H.sub.2 ], and assuming that hydrogenation of the nitrile is the rate limiting step in the above sequence, that k.sub.r &lt;&lt;k.sub.i. These requirements place a heavy burden on the requirements for the catalyst used in selective hydrogenation-hydrolysis of cyanohydrins, but even this requirement is augmented by the need for the catalyst to be active at relatively low reaction temperatures since the cyanohydrins are not particularly thermostable, by the need for the catalyst to be relatively resistant to poisoning by nitro-containing organic materials, and by the need for the catalyst to be hydrothermally stable at the low pH required for this transformation.
Previously this need has been met, virtually uniquely, by a catalyst of zerovalent palladium supported on barium sulfate. As a zerovalent metal active at low temperatures in the reduction of nitriles, palladium is relatively resistant to poisoning by organic nitrogen-containing compounds, especially amines. By working in a restricted pH range it was possible to favor hydrolysis of the imine to the aldehyde, and by performing the reaction over a limited temperature range it was possible to minimize the decomposition of reactants so as to give a process yielding the desired product aldehyde at commercially acceptable levels; see U.S. Pat. No. 4,581,447. However much of an improvement our previous work may have been over its predecessors, a "wish list" of further improvements had as its top priority development of a continuous process for the hydrogenation of cyanohydrins, preferably using a fixed bed of catalyst, and it was soon appreciated that catalysts suitable for batch hydrogenation were eminently unsuitable for fixed bed hydrogenation.
Barium sulfate is an unusual support material for catalysts but is used to support palladium in the hydrogenation of cyanohydrins because it attenuates the activity of zerovalent palladium sufficiently to impart selectivity in the hydrogenation of the relevant functional groups, but not so much as to make the palladium unusable in the 10.degree.-50.degree. C. range. However, barium sulfate generally is available only as a fine powder, which is wholly unsuitable for use in a fixed bed. Furthermore, and more importantly, it was found that even in batch reactions palladium on barium sulfate deactivates very quickly. Rarely could the palladium on barium sulfate catalyst be reused, and occasionally it even became deactivated prior to completion of the batch reduction. In developing a method of continuously and selectively converting cyanohydrins to their corresponding aldoses it quickly became apparent that a new catalyst needed to be developed.
In developing a new catalyst system zerovalent palladium seemed to be the most reasonable choice as the catalytically active metal. However, the prior art gave no guidance as to the choice of support. What is required for a successful continuous process is that the catalyst be (1) selective as described above, (2) be active in the 10.degree.-50.degree. C. range, (3) be physically and chemically stable under conditions of low pH, and (4) be long lived, that is, exhibit relatively low deactivation with continued use. We have found that zerovalent palladium supported on certain organic polymers has all of these requisite properties, and a continuous method of reducing cyanohydrins to their corresponding aldoses now is a reality.
Catalysts of palladium and organic polymeric supports are relatively well known. Most are in a class that may be described as polymer bound palladium, that is, heterogeneous analogs of homogeneous palladium catalysts. In this approach palladium has been bonded to a resin, such as a chloromethylpolystyrene, via complexing with ligands covalently bonded to polystyrene. Although this class of palladium-organic polymer catalysts has received more attention, it is not the class of catalysts found to be successful in practicing our invention. Another class of palladium catalysts utilizes organic polymers for the dispersion of zerovalent palladium. In this approach the polymer provides only a physical structure and a surface on which zerovalent palladium may be more or less uniformly dispersed, and it is this class of polymer-supported zerovalent palladium which has been demonstrated to be successful in our invention. Exemplifying palladium dispersed on polystyrene is U.S. Pat. No. 4,127,594, where the catalyst is used for removing impurities as .beta.-chloroacrolein from epichlorohydrin. Inui et al., J. Mol. Catal., 22(1), 93 (1983) describes the use of palladium dispersed in a polymer matrix, including a blend of poly(ethylene oxide) and polystyrene, for the gas phase hydrogenation of ethylene. Lisichkin et al. in Chem. Abst., 83(7): 57968q used palladium stabilized with polystyrene as a catalyst in the liquid phase hydrogenation of 1-hexene at 30.degree.-50.degree. C. Only a polymer bound palladium catalyst appears to have been used in dehydrogenation of a nitrile, and in that sole example only an aromatic nitrile was reduced. N. L. Holy, J. Chem. Soc., Chem. Commun., (23), 1074 (1978).
We have found that zerovalent palladium dispersed on certain organic polymers are effective catalysts for the selective conversion of cyanohydrins to their corresponding aldehydes via concurrent hydrogenation-hydrolysis. The resulting catalysts exhibit high selectivity with good activity at 10.degree.-50.degree. C. The catalysts have excellent physical and chemical integrity at conditions of low pH where the transformation is performed, and are quite resistant to poisoning and to deactivation generally.